Method and apparatus for creation of drug delivery and/or stimulation pockets in myocardium

ABSTRACT

An apparatus and method for creating drug-filled pockets within muscle tissue, such as myocardium of the heart for increasing angiogenesis. More particularly, the apparatus has an excising assembly with a dilator tip for penetrating and advancing through the surface and body of a muscle or organ, such as the heart. Preferably, the dilator tip has a low level laser optical fiber emission to ease the passage of the excising assembly and provide thermal damage which also stimulates angiogenesis. More preferably, the dilator tip also disperses a pharmacologically active substance as the apparatus is passed through the tissue and/or creates pockets. The excising assembly is connected to a hand-held control device from which the operator pushes a switch to activate a punching mechanism within the excising assembly. The punching mechanism cuts a discrete piece of muscle tissue and traps it within the excising assembly leaving a pocket in the remaining muscle tissue. The excising assembly may also optionally release a bolus of the pharmacologically active substance into the pocket so created. Most preferably, there is a timing mechanism to measure the contraction of the heart, and the timing mechanism is synchronized with the operator&#39;s switch on the hand-held device to ensure that the punching occurs at maximum contraction of systole. A measurement guide determines how much excised tissue is trapped in the reservoir of the excising assembly. At a threshold level of filling, the surgeon will remove the excising assembly from the hand-held control device and open the punching mechanism for release of tissue. More preferably, the threshold level of filling will automatically turn off the switch to the punching mechanism to indicate to the surgeon the need to empty the excising assembly of tissue.

This application is a divisonal of pending U.S. patent application Ser.No. 08/773,778 entitled Method and Apparatus for Creation of DrugDelivery and/or Stimulation Pockets in Myocardium, Filed Dec. 26, 1996.

FIELD OF INVENTION

This invention relates to the field of microsurgery in creating pocketspaces within muscle tissue, and more particularly to creatingintramyocardial pockets for the purposes of drug delivery and/orstimulation of angiogenesis of the myocardium of the heart.

BACKGROUND OF THE INVENTION

Various surgical techniques have been developed to counteract ischemicconditions of the heart, including coronary bypass grafts, angioplastyand for patients who are not suitable candidates for these procedures,or in conjunction with these procedures, transmyocardialrevascularization (TMR). In TMR generally, the surgeon creates manynarrow channels of approximately one millimeter width that span from anopening at the endocardial surface of a ventricle of the heart,preferably the left ventricle, into the myocardium and then terminatingbefore the epicardial surface. The surgeon generally uses laser tocreate the channels by either accessing the endocardium through apercutaneous route or the epicardium through an incision into the chestwall. The pressure within the left ventricle at systole forcesoxygenated blood into the channels and consequently oxygenates theischemic myocardium of the left ventricle. Methods of TMR using laser, acombination of laser and mechanical, and solely mechanical apparatushave been disclosed in the prior art, including United States patentssuch as U.S. Pat. Nos. 4,658,817 (Hardy), 5,125,926 (Rudko, et al) and5,380,316 and 5,389,096 (Aita, et al) and also more recently inco-pending applications Ser. No. 08/607,782 and Ser. No. 08/713,531.

The percutaneous method does not require the epicardium to beperforated. The surgical method through incision into the chest walldoes require perforation of the epicardium to create channels throughthe myocardium and endocardium which may result in increased peri- andpost-operative bleeding. Recent methods described in pending applicationSer. Nos. 08/607,782 abd 08/713,531, however, provide for initialmechanical piercing of the epicardium prior to ablation of myocardialand endocardial tissue by laser which reduces bleeding from the channelsinto the chest cavity.

A current limit of TMR in revascularizing myocardial tissue includespost-operative closure of a significant proportion of the channels. Withlittle success, attempts have been made by practitioners to maintain thepatency of the lumen of the channels through administration ofappropriate pharmacologically active compounds. Maintaining a sufficientconcentration of such compounds within the channels is very difficultconsidering the channels are exchanging circulation with the high bloodvolume interchange of the left ventricle.

TMR's effectiveness in revascularizing ischemic myocardial tissueresults not only from the introduction of oxygenated blood into themyocardium through the created channels, but through the increase inangiogenesis in the myocardial tissue surrounding the channels secondaryto localized immune-mediated responses. Co-pending application Ser. No.08/664,956 describes the advantage of creating channels and pocketsintramyocardially in stimulating angiogenesis of the myocardium by usinglaser supplemented optionally with mechanical means. The pockets orchannels do not need to be patent at the endocardial surface at creationnor remain patent over time for the angiogenesis stimulation to beeffective. The stimulation of angiogenesis occurs through localizedimmune mediated response to the tissue trauma resulting in an influx ofblood borne growth and healing factors and stimulation of capillarygrowth surrounding the pockets or channels. The oxygenation ofmyocardial tissue and the functioning capacity of the heart are therebyincreased significantly. It is desireable, therefore, to provide aneffective concentration of pharmacologically active angiogenic compoundsto the myocardium to stimulate angiogenesis on a supplementary orindependent basis for the same drug delivery problems as discussedabove.

Methods have been disclosed in certain of the above cited art forremoving myocardial tissue through laser emission ablation or mechanicalcutting techniques to create channels and/or pockets for myocardialrevascularization purposes. A noted advantage of using a mechanicalcutting tool over the laser method is the ability to cut and remove adiscrete piece of tissue. In addition, less bleeding occurs with the useof mechanical as verses laser perforation of the epicardium.

An advantage of using laser over the mechanical method is the reductionin force necessary to pierce the surface and advance through the body ofa muscle, and more particularly, piercing the epicardium and advancingthrough myocardial tissue. The reduction in force allows the surgeongreater ease and control over the procedure. An additional advantage oflaser over mechanical surgery is that thermal as compared to mechanicaltrauma of tissue results in less peri- and post-operative bleeding, lessconsequential tissue tearing with consequential post-operative fibrousscarring, and potentially greater post-operative immune-mediatedreactive angiogenesis.

Methods have been disclosed in certain of the above cited art forsynchronizing the laser emission of TMR with the heart beat (as measuredby EKG) of the heart (U.S. Pat. No. 5,125,926 (Rudko, et al). Thesesynchronization efforts were made in the attempt to time the emission ofthe laser with the electrically quiet period of the heart to reduce theoccurence of arrhythmias. The peaks of the EKG waves reflect theelectrical conductance of the heart, however, and therefore do notdirectly match the actual contraction of the musculature of the heart.Methods have not been disclosed for synchronizing, directly orindirectly, pocket formation with the contraction of the heart.

The above methods and apparatus and discoveries to date have notprovided for concomitant administration of pharmacologically activesubstances to the channels and/or pockets at their creation. It istherefore desirable to provide an apparatus and method for makingdistinct pockets within muscle tissue, and in particular, themyocardium, for controllable drug delivery for purposes, among others,of increasing the patency of myocardial channels and/or increasingangiogenesis in the surrounding myocardial tissue. It is furtherdesirable to provide an apparatus and method that simultaneouslycombines the use of laser and mechanical means to maximize theadvantages and minimize the disadvantages of each. Such an apparatus andmethod is easily controlled by a surgeon, administers moderate thermaldamage reducing reactive bleeding and fibrous scarring and increasingreactive immune-mediated localized angiogenesis, cleanly removes allexcised tissue, and concomitantly optionally delivers substances orinserts containing pharmacologically active compounds into the formedpocket. It is also further desired to provide an apparatus and methodfor directly synchronizing the timing of the pocket formation with thecontraction of the heart.

SUMMARY OF THE INVENTION WITH OBJECTS

Broadly, an advantage of the present invention is to provide anapparatus and method for creating pockets within muscle tissue forpurposes of stimulation and/or delivering substances containingpharmacologically active compounds.

More specifically, an advantage of the present invention is to providean apparatus and method for creating pockets within the myocardium ofthe heart, for purposes of stimulation and inserting substances in thepockets that concomitantly are effective in stimulating angiogenesis insurrounding myocardial tissue and/or maintaining the patency of anynearby TMR created channels.

Another advantage of the present invention is to provide an apparatusand method for cleanly removing a distinct piece of tissue from an organor body tissue through a mechanical punching means thus reducing thelikelihood of consequential emboli.

Another advantage of the present invention is to provide an apparatusand method using a reservoir means for storing the excised tissue toallow multiple pockets to be successively created without interruptionfor removal of excised tissue all using the same apparatus.

Another advantage of the present invention includes providing ameasurement device for setting the distance within the muscle tissue atwhich the tissue shall be excised.

Another optional advantage of the present invention includes providingan apparatus and method using a leading laser tip delivering low levelthermal damage to reduce the force necessary for piercing of theepicardium and advancing the tool through or into the myocardium. Theapparatus is thereby easier to control and manipulate by the surgeon,causes less bleeding at the epicardial surface than using a higher powerlaser and less fibrosis overall than using a mechanical piercing tool,and provides supplemental angiogenic stimulation by thermal damage ofthe myocardium.

An additional advantage of the invention is to provide an apparatus andmethod with a timing mechanism allowing the punching means to open andthen rapidly close at the highest point of contraction at systolethereby allowing tissue to enter the gap created by the openinginitially and then cutting the tissue within the gap which controls thesize of tissue removed and reduces the arrhythmic side effects ofremoving the tissue. A further advantage is to have the timing mechanismdirectly reflect the contraction of the muscle by means of a pressuremeasurement.

A further advantage of the present invention is providing a method andapparatus for drug delivery to introduce substances with at least onepharmacologically active compound into the pockets and/or channelscreated. More particularly, an advantage of the invention includesproviding a continuous flow drug delivery means and/or a pulsed drugdelivery means where the pulsed drug delivery means introduces a bolusof substance timed and directed to release at the location and moment ofpocket creation.

The present invention comprises a method and apparatus for creatingpockets containing substances with pharmacologically active compoundswithin muscle tissue. One example of muscle tissue where the method anduse of the apparatus is very applicable is ischemic myocardial tissue inneed of high localized concentrations of angiogenic factors. Otherexamples include tumors and bone.

A mechanical excising device including a tapered dilator tip combinedwith an elongated flexible low-powered lasing apparatus at the dilatortip, such lasing apparatus including at least one optical fiber, isinserted via surgical incision and guided to the location exterior tothe designated organ or body tissue to be treated. For example, withtreating the myocardium of a ventricle of the heart, the device isinserted into the chest cavity of a patient and guided to an areaexterior to the ventricle. The low-powered optical fiber lasingapparatus at the dilator tip of the device is activated and disperseslow level thermal trauma upon contact thus reducing the force necessaryto advance the dilator tip through the epicardium and myocardium tocreate a tunnel passage for the device. The thermal damage also reducesthe overall bleeding in the myocardium and the tendency towards fibrosiswith mechanical trauma, and increases the stimulation of angiogenesis inneighboring myocardial tissue.

The surgeon advances the excising tool to a designated distance by meansof a hand-held control device. The excising tool is connected to thehand-held control device, and its attachment is secured by a trap slidemeans. A synchronized timing means (for example, an intramyocardialpressure detector or an EKG), optionally is synchronized with thehand-held control device to determine the opening and closing of thepunching mechanism of the excising tool allowing myocardial tissue toenter the gap created by the opening and then be cut by rapid closure ofthe sharpened edges of the punch at maximum contraction at systole, thuscreating a pocket within the tissue. The synchronized timing meanspreferably is a pressure detector located on the surface of the excisingtool and connected with a power means for activating the punchmechanism. An insertion means within the device optionally introduces asubstance, preferably containing a pharmacologically active compound,into the pocket to maintain a sufficient concentration of such acompound within the localized tissue. Such insertion means may be acontinuous flow mechanism and/or be simultaneously triggered to delivera bolus of the substance into the pocket with punch closure. Forexample, for intramyocardial pockets, an angiogenic compound such asVEGF may be inserted into the pockets to increase the angiogenesiswithin surrounding myocardial tissue. The device will then be movedwithin the myocardium to optionally create another intramyocardialpocket.

The advancement or withdrawal of the excising tool through themyocardium will be measured by a depth guide located on the surface ofthe excising tool. More particularly, the surgeon may optionally advancethe excising tool through the myocardium and endocardium to the point ofentry into the ventricle whereupon the surgeon will detect thesignificant reduction in pressure necessary to advance the tool. At thispoint, the surgeon may optionally withdraw the excising tool through themyocardium, creating pockets at designated depths along its path.Alternatively, the surgeon may optionally have already created pocketson the advancement of the excising tool through the myocardium,obviating the need to create pockets upon its withdrawal. The pocketsare created by the Surgeon's trigger of a release button on thehand-held control device and coordinately also based on the synchronizedtiming mechanism.

The excised tissue is trapped within a reservoir means within theexcising tool. With closure of the punching mechanism, the trappedtissue is compressed into the reservoir. Optionally, a means ofmeasuring the filling of the reservoir is provided on the hand-heldcontrol device. Alternatively, after a set number of punches, forexample five, the surgeon may manually empty the reservoir means or theexcising tool may automatically require resetting mandating an emptyingof the reservoir outside the body. The reservoir means may be emptiedupon complete removal of the excising tool from the chest cavity,opening of the punching mechanism, forward expulsion of the tissue outof the opening by a plunger means within the excising tool and brushingoff the extruding tissue. The foregoing methods of handling the excisedtissue allows for the process of creating multiple pockets for drugdelivery within each channel passage of the tool through the myocardium.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a heart, partly in section, showing adevice for creating a drug-filled pocket.

FIG. 2 is a view of an excising assembly portion of the device in FIG. 1with its punching mechanism open as connected to a combined opticalfiber/insertion cable.

FIG. 3A is a view of the cross section of the distal end of the combinedfiber/insertion cable.

FIG. 3B is a view of the distal end of the combined opticalfiber/insertion cable.

FIG. 3C is a view of the distal end of the tapered dilator tip includingthe combined optical fiber/insertion cable.

FIG. 4 is a partial longitudinal section view of the device of FIG. 1showing the excising assembly as it is connected to a hand-held controldevice.

FIG. 4A is a diagram showing how a punching mechanism of the device inFIG. 4 is enabled by a synchronized timing means and an operator'sswitch.

FIG. 5 demonstrates the corresponding wave patterns of an EKG and apressure transducer.

FIG. 6A is an outside view of the hand-held control device of FIG. 4showing a locking trap slide in its open position and the combinedfiber/insertion cable for inserting into the excising assembly.

FIGS. 6B-6C demonstrates how the excising assembly of FIG. 2 is insertedinto the hand-held control device of FIG. 4 and locked into place.

FIG. 7 is an outside view of the pump controller and syringe, the sourceand pumping unit for the substance that is delivered through theexcising assembly.

FIG. 8 demonstrates how the pump controller dispenses the substance fordelivery into the combined fiber/insertion cable.

DETAILED DESCRIPTION OF EMBODIMENT

With reference to the drawing, FIG. 1 diagrammatically depicts a humanheart with the epicardium 12 of the left ventricle 14 exposed where astimulation/drug pocket formation procedure according to the inventionis to be performed. Preliminary to the procedure, the surgeon makes anincision in the patient's chest to expose the outer wall (epicardium) ofthe heart's left ventricle. In a human heart, the wall of the leftventricle is comprised of an outer layer, the epicardium 12, the mainmuscle thickness, the myocardium 13, and the inner layer or endocardium15. The epicardium is comprised of a smooth moist serous membrane whichis somewhat tougher than the other tissue layers of the heart muscle.

In accordance with the method of the present invention, the surgeon usesa hand-held control device 16 attached to an excising assembly 17 whichis manipulated and operated to form a series of drug filled stimulationpockets 18 in the myocardium of the patient's heart at selected spacedapart locations. As will be described in greater detail below theapparatus 19 for creating pockets has an excising assembly 17 attachedto a hand-held control device 16. As seen in FIG. 4, the proximalportion of the excising assembly 17 sits within the distal portion ofthe hand-held control device 16 and its placement is secured there by alocking slide trap 5. The locking slide trap 5, as seen in FIGS. 6A, 6Band 6C, slides along an opening 6 on the superior distal aspect of thehand-held control device 16. The locking slide trap 5 optionally mayhave one or more indentations 8 on its inferior surface that snap andconnect with one or more protrusions 9 on the superior distal aspect ofthe hand-held control device 16. Once locked inside the hand-heldcontrol device 16, the excising assembly 17 optionally protrudes outwardin a distal direction from a range of 3-5 cm.

The excising assembly 17 has a tapered dilator tip 21 optionally havinga distal end of an optical fiber means 20, preferably a bundle of fibers(see FIG. 1), which extends through the excising assembly 17 and thehand-held control device 16. The optical fiber means 20 may be of anydesign and may include single fibers as well as the preferred bundle offibers. The tapered dilator tip 21 optionally has a length of about 1 to2 mm. The excising assembly 17 also has a measurement scale 41 on itssurface to indicate its depth of penetration within tissue. The proximalend of the optical fiber means 20 is connected to a source or generator22 of laser energy which is preferably a Holmium laser that operates ata wave length in the range of 1.8-2.2 microns, a pulse frequency in therange of 2-25 Hertz and a power level range of approximately 0.6 J to1.65 J, or an excimer laser may be used as well as other suitablemedical lasers. This type of laser is preferable because it provideshigh absorption efficiency, hemostasis and a moderate absorption rangein myocardium tissue, and is compatible with optical fiber delivery. Theactivated laser emitting a low-level energy laser beam through thedistal end of the optical fiber means 20 provides a low energy ablationof tissue to ease the advancement of the dilator tip and excisingassembly to pierce through the epicardium and tunnel through themyocardium. The laser is activated by depression of a foot switch whichis connected to the power generator responsible for powering the lasersource 22.

At the laser generator, laser energy is supplied to the optical fibermeans 20 which, at its distal end, as shown in FIG. 2, has a diameter ofaround 0.08-0.2 mm. The optical fiber means may be either a single fiberor comprised of a plurality (e.g. FIGS. 3A to 3C) of smaller glassfibers. The optical fiber means is optionally surrounded by a suitableplastic material 34, such as 353 ND Epoxy, which protects the glassfiber and is particularly useful in holding together multiple glassfibers. Near its distal tip, the bundle preferably is surrounded by anannular tantalum marker 36 which serves to retain the bundle closelypacked in a proper geometric boundary. The layer surrounding the annulartantalum marker 36 and/or the plastic material 34 comprises asubstance-filled cylindrical shell insertion means 35, preferably madeof plastic such as polypropylene, having a wall thickness of 0.008 mmand equidistantly surrounding the optical fiber means 20 at a distancesuitable to allow for delivery of drugs in the space (37) between theoptical fiber means 20 and the shell 35. The optical fiber means 20described is for purposes of illustration only and it will be recogizedby those skilled in the art that single fibers and other laser deliverysystems may be used. The optical fiber means 20 and the substance-filledcylindrical shell insertion means 35 as described above run together asthe combined optical fiber/insertion cable 45.

The substance within the cylindrical shell insertion means 35 preferablycomprises a fluid with at least one pharmacologically active compound ora flushing/cooling liquid such as a saline solution. The substance ispropelled distally in the space 37 within the cylindrical shellinsertion means 35 due to positive pressure from the source of thesubstance which location preferably is at the proximal end of thecylindrical shell insertion means 35. The substance is delivered to thetissues along the channels and pockets in the muscle created by theexcising assembly through ports 38 in the cylindrical shell insertionmeans 35. The ports 38 are preferably located slightly proximal to thedistal tip of the optical fiber means 20 and, if present, the annulartantalum marker 36, see FIGS. 3A, 3B and 3C.

An optional source of the substance is a syringe 72 located in a pumpcontroller 71 as seen in FIGS. 7 and 8. The syringe 72 fits within asyringe hold 70 within the pump controller 71. The plunger 81 of thesyringe 72 could optionally have a screw 80 at its distal end which isturned moving the plunger 81 forward into the syringe 72 by a step motor77 within the pump controller 71. For example, a black box 78 isconnected to and powers the step motor 77 to rotate in direction A (asseen in FIG. 8) which causes the screw 80 to move in direction B. As theplunger 81 is moved distally within the syringe 72, the substance 85within the syringe 72 is dispensed into a tubing 82 which ends in a Tshaped junction 79. The combined optical fiber/insertion cable 45 runswithin the top of the T shaped junction 79 of the tubing 82. The ends ofthe T shaped junction 79 are sealed around the combined opticalfiber/insertion cable 45 by some sealing means, for example, glue atposition 86. Inlet ports 84 of the cylindrical shell insertion means 35of the combined optical fiber/insertion cable 45 allow for the inflow ofthe substance 85 from the tubing 82 within the T junction 79. Thecylindrical shell insertion means 35 is sealed at a point 87 that isproximal to the inlet ports 84. The substance 85, therefore, moves in adistal direction within the cylindrical shell insertion means 35 towardsthe excising assembly 17. A sleeve 83 covers the T junction 79 tofurther support the integrity of the connection between the tubing 82and the cylindrical shell insertion means 35 of the combined opticalfiber/insertion cable 45.

The pump controller 71 has a drug delivery selection setting 74 on itssurface to activate the pumping of the substance 85. As seen in FIG. 7,the drug delivery selection setting 74 could optionally provide settingsfor off (1), pump while lasing only (2), pump while punching pocketsonly (3) and pump while lasing and punching pockets (4). A speed setting73 for the step motor 77 is also located on the surface of the pumpcontroller 71. The speed setting 73 allows for 1) the stepping motorsrate to be determined in cases of continuous flow of the substance, forexample the step motor 77 turns at x steps per second, and 2) the numberof steps to create a certain size drop of the substance 85, for example,large drops (5-20 steps) and small drops (1-3 steps). An incomingelectrical wire 75 carries signal input to the black box indicating thetiming of the laser and the punch of the excising assembly 17. Anoutgoing electrical wire 76 connects to a power source for powering thepump controller 71.

As seen in FIG. 2, the excising assembly 17 comprises two semi-dividableshell portions (distal 21 and proximal 48) unified by a common centralrigid hollow cylinder 46 running the full length of the longitudinalaxis of the excising assembly 17. The common central rigid hollowcylinder 46 extends beyond the span of the two shell portions (21 and48) and ends proximally with the proximal end of a solenoid connectorflange 53. The solenoid connector flange 53 comprises a relatively shortcylindrical shell surrounding the common central rigid hollow cylinder46 at the proximal end of the excising assembly 17. The common centralrigid hollow cylinder 46 carries the combined optical fiber/insertioncable 45 within it from the distal through the proximal end of theexcising assembly 17.

A tapered dilator tip 21, the distal semi-dividable shell portion of theexcising assembly 17, has a proximal end comprising a closed surfacelying flush against the common central rigid hollow cylinder 46 and hassharp edges along the perimeter of said proximal end. Areservoir/plunger portion 48, the proximal semi-dividable portion of theexcising assembly 17, comprises two encircling cylindrical shell units(inner 51 and outer 49) further encircling the common central rigidhollow cylinder 46, and a control device flange 50.

The outer shell unit 49 comprises a rigid hollow cylinder of stainlesssteel having a diameter range of 0.5 to 2.0 mm having an open distal endwith sharp edges and an open proximal end. A control device flange 50comprising a rigid cylindrical shell is attached to the proximal end ofthe outer shell unit 49. The control device flange 50 connects in aremovable manner the excising assembly 17 to the hand-held controldevice 16. The distal and proximal ends of the control device flange 50preferably comprise closed surfaces to the point of their attachmentwith the outer shell unit 49 and the proximal end of the outer shellunit 49, respectively.

A cylindrical plunger 51, the inner cylindrical shell unit, has an outercylindrical surface lying flush against the inner surface of the outershell unit 49 and an inner cylindrical surface lying flush against theouter surface of the common central rigid hollow cylinder 46. Eachsurface of the cylindrical plunger 51 slides easily along the othersurface it opposes. The distal and proximal ends of the cylindricalplunger 51 comprise closed surfaces. The distal end of the cylindricalplunger 51 preferably lies in its relaxed position somewhat proximallyto the distal end of the outer shell unit 49. The proximal end of thecylindrical plunger 51 preferably protrudes in its relaxed positionbeyond the proximal end of the control device flange 50. Near itsproximal end, the cylindrical plunger 51 has a slotted grooveindentation 52 on its outer cylindrical surface. The cylindrical plunger51 upon pressure applied to either of its ends can slide longitudinallywithin the outer shell unit 49 and along the common central rigid hollowcylinder 46. Upon pressure at its distal end, the cylindrical plunger 51moves proximally within the outer shell unit 49 to create a reservoirmeans 44 for containing excised tissue. (See FIG. 2).

Upon a punch signal from the hand-held control device 16, the dilatortip portion 21 separates from the reservoir/plunger portion 48 to createa gap into which muscle tissue enters and then both semi-dividableportions close rapidly at their sharp edges. In this manner, the twosemi-dividable portions of the excising assembly 17 operate as a punchto cut the muscle tissue. The punch signal is activated by a dualmechanism within the hand-held control device 16.

As seen in FIGS. 4 and 4A, a black box 65 within the hand-held controldevice 16 preferably is connected to a synchronized timing means forsensing contractions and expansions of the beating heart. Preferably,the synchronized timing means comprises a pressure transducer 63, forexample a thin film piezo electric pressure transducer, which optionallyis located on the outer surface of the outer shell unit 49, andpreferably the distal section of the outer shell unit 49, and electricwiring 64 connected to the pressure transducer distally. The electricwiring 64 runs proximally within the common central rigid hollowcylinder 46 into the hand-held control device 16 and to the black box65. Optionally the sychronized timing means may be an EKG with signalinput to the black box 65.

Upon receiving the signal from the synchronized timing means, acomparison circuit within the black box 65 identifies the point ofbeginning systole (comparable to the peak of the R wave on an EKG, seeFIG. 5 ). The solenoid powered forward may alternatively open or bothopen and close the punch mechanism by enabling a punch button switch 66within the hand-held control device 16. In the first case, optionallythe punch mechanism would open at beginning systole (e.g. maximum of Rwave on the EKG) or at a threshold level of contractible pressure (e.g.maximum of P wave less 25%), and then close with the solenoid's reverseat a set time within the contraction, or preferably at the peak ofcontraction (S wave on the EKG or maximum of P wave on the pressuremeasurement). In the second case, the open/close action of the punchwould occur sometime during systole, and preferably at a threshold ofcontractile pressure as discussed above. The punch button switch 66 mustalso be enabled from an operator's depression of a push button 42 on thesurface of the hand-held control device 16. With the enablement fromboth the black box 65 and the push button switch 66, a signal is sent toa circuit board 68 which powers a solenoid 62 forward to operate thepunch mechanism of the excising assembly 17 optionally opening it (asexampled above) at the point of beginning systole (peak of the R wave onan EKG) or at a minimum threshold of pressure and closing it at maximumcontraction of systole (peak of the S wave on an EKG or the pressurewave peak, P, on a pressure transducer measurement scale, see FIG. 5).The source of electrical energy to the black box is from an adjacentbattery 69.

The powered forward solenoid 62 propels a solenoid/flange connector 67distally for approximately 1-3 mm within the hand-held control device 16and then (or optionally with the solenoids reversal) pulls it backproximally in a rapid movement. The distal movement of thesolenoid/flange connector 67 is optionally synchronized to occur at thepoint of beginning systole or at a minimum threshold of pressure and theproximal movement at the point of maximum contraction of systole. Thesolenoid/flange connector 67 has a slotted groove on its surface forholding part of the solenoid connector flange 53 of the excisingassembly 17. The distal movement of the solenoid/flange connector 67therefore also distally propels the common central rigid hollow cylinder46 and its attached dilator tip portion 21, thereby opening a gapbetween the two semi-dividable portions (21 and 48) of the excisingassembly 17 the same distance allowing myocardial tissue to enter thegap. At a certain point during systole, for example, maximum contractionof systole, the dilator tip portion 21 is rapidly pulled back to closeupon the reservoir/plunger portion 48 thereby operating the punchingmechanism to excise myocardial tissue and trap the tissue within thereservoir means 44.

The tissue trapped in the reservoir means 44 pushes up against thedistal end of the cylindrical plunger 51, thereby sliding thecylindrical plunger 51 and its slotted groove indentation 52 in aproximal direction. As seen in FIGS. 4 and 6A, an excised tissueejection indicator 60 on the hand-held control device 16 has a crosspiece 61 that aligns with the inferior aspect of the slotted grooveindentation 52. As the slotted groove indentation 52 moves proximally,so does the cross piece 61 thereby showing on the excised tissueselection indicator 60, the amount of excised tissue trapped within thereservoir means 44. Removal of the excising assembly 17 from thehand-held control device unit, allows for greater ease in forcing thecylindrical plunger 51 distally through the reservoir means 44 torelease the trapped excised tissue.

Upon the operator's release of the push button switch 67, the solenoid62 is reversed to allow it to be powered with the next doubly-enabledsignal. Optionally, upon the solenoid's 62 reverse, the pump controller71 is activated to send a bolus of pharmacologically active substance 85through the tubing 82 and the cylindrical shell insertion means 35 toits distal open end at the tip of the dilator tip portion 21 which ispositioned within the created pocket cavity upon its creation.

A surgeon by activating a laser switch, preferably a foot switch,activates laser emission through the optical fiber means 20 anddepending on the position chosen on the drug delivery selection setting74, the continuous flow of the pharmacologically active substancethrough the cylindrical shell insertion means 35. The surgeon thenadvances the excising assembly 17 through the epicardium 12 and into themyocardium 13. The surgeon passes the excising assembly 17 through thepassage created, firing a punch button 42 on the hand-held controldevice 16 which thereby activates the punching mechanism within theexcising assembly 17 to cut and store an excised piece of tissue andcreate an intra-myocardial pocket. Preferably a substance is releasedthrough the portal of the cylindrical shell insertion means 35 at thedistal end of the dilator tip portion 21 of the excising assembly 17 ona continuous-flow and/or bolus flow basis where the bolus of morepreferably a pharmacologically active substance, for example VEGF, isreleased into the newly created pocket. A drug-filled pocket is therebyproduced.

Preferably, the surgeon first passes the excising assembly 17 throughthe epicardium 12, myocardium 13 and endocardium 15 to enter theventricle 14 whereupon the reduction in resistance met with furtheradvancement of the excising assembly indicates to the surgeon the depthof the endocardium and the thickness of the heart wall relative to themeasurement scale 41 on the surface of the excising assembly 17. Thesurgeon may alternatively withdraw the excising assembly 17 through thepassage created firing the punch button 42 at designated distanceswithin the wall of the myocardium 13 as measured on the measurementscale 41 during the withdrawal. The surgeon thereby creates drug filledpockets at designated depths within the myocardium.

Upon full retraction of the excising assembly 17 from the ventriclewall, the surgeon will continue with subsequent entries into themyocardium until the punch (the two semi-dividable portions of theexcising assembly 17) dulls or the excised tissue ejection indicator 60indicate the reservoir means 44 is full. At that point a change ofexcising assembly 17 for cleanout or sharpness will be done.

FIGS. 6A through 6C, demonstrate how the excising assembly 16 isconnected in a removable manner to the hand-held control device (16).The combined optical/insertion cable 45 is threaded from the hand-heldcontrol device (16) into the proximal end of the common central rigidhollow cylinder 46 of the excising assembly 17. Optionally theelectrical wire 64 for the pressure transducer 63, runs along the outersurface of the outer shell unit 49 to connect to 360 degree contactstrips on the surface of the control device flange 50, which uponcontact with the housing in the hand-held control device 16, conductssignals to the black box 65 within the hand-held control device. Theexcising assembly 16 is then inserted into the hand-held control device16 while the trap slide 5 of the hand-held control device 16 is in itsopen position. Once the excising assembly 17 is in its proper positionwithin the hand-held control device 16, then the trap slide 5 is pusheddistally to lock it closed by snapping the indentations 8 on the lockingtrap slide 5 into the protrusions 9 on the hand-held control device 16,and thereby securing the excising assembly 17.

As will be understood by those familiar with the art, the presentinvention may be embodied in other specific forms without departing fromthe spirit or essential characteristics thereof. The scope of thepresent invention is therefore limited only by the scope of the claimsappended hereto.

What is claimed is:
 1. An apparatus for creating pockets within muscle tissue, the apparatus comprising: at least one generally cylindrical excising assembly for entering through and excising muscle tissue having a tapered dilator tip at a distal end; and a hand-held control means for determining the position and timing of the tissue excision.
 2. The apparatus of claim 1 wherein the excising assembly further comprises two semi-dividable shell portions encircling a common central core cylinder running the longitudinal axis of the excising assembly and carrying the insertion means, where the distal semi-dividable shell portion comprises the tapered dilator tip having a closed surface at its proximal end and sharp edges along the perimeter of said proximal end, and the proximal semi-dividable shell portion comprises two encircling cylindrical shell units, the outer shell unit comprising a hollow cylinder having an open distal end with sharp edges and an open proximal end attached to a connector flange means for connecting the excising assembly to the hand-held control means, and the inner shell unit comprising a cylindrical shell plunger means, said cylindrical shell plunger means comprising an outer cylindrical surface lying flush against the inner surface of the outer shell unit, an inner cylindrical surface lying flush against the outer surface of the central hollow core cylinder, a closed distal end lying in its relaxed position near the distal end of the outer shell unit, and a closed proximal end protruding slightly in its relaxed position beyond the proximal side of the connector flange means, said cylindrical shell plunger means being capable of sliding within the outer shell unit upon pressure applied to either of the shell plunger ends.
 3. The excising assembly of claim 2, where by a signal from the hand-held control means, the semi-dividable shell portions separate to let muscle tissue enter into the opening created, and then close rapidly at their sharp edges to operate as a punch to cut the muscle tissue, and wherein the tissue trapped within the excising assembly pushes up against the distal end of the cylindrical shell plunger means, thereby sliding the cylindrical shell plunger means in a proximal direction to protrude further beyond the connector flange means allowing by amount of said protrusion an indication of how much tissue has been trapped within the excising assembly.
 4. The apparatus of claim 1 further comprising an optical fiber means that longitudinally runs through the common central core cylinder of the excising assembly having at least one proximal end connected to a source of laser energy and at least one distal end at the tapered end of the dilator tip for advancing the dilator tip through the surface and into the interior of the muscle by thermal damage.
 5. The apparatus of claim 3, wherein the semi-dividable shell portions abutting each other with opposing sharp edges can separate to a certain distance of approximately 1 to 9 mm.
 6. The apparatus of claim 2 also comprising an insertion means for introducing substances into the pockets created.
 7. The apparatus of claim 6 wherein the insertion means comprises a continuous flow mechanism distributing substances at a continuous steady rate.
 8. The apparatus of claim 6 wherein the insertion means comprises a pulsed flow mechanism distributing substances in boluses.
 9. The apparatus of claim 6 wherein the insertion means comprises both a continuous flow mechanism and a pulsed flow mechanism for distributing substances.
 10. The apparatus of claim 6 wherein the substance comprises at least one pharmacologically active ingredient.
 11. The apparatus of claim 10 wherein the substance comprises at least one angiogenic factor.
 12. The apparatus of claim 10 wherein the substance comprises at least one compound for maintaining the patency of channels or pockets within muscle tissue.
 13. The apparatus of claim 1 further comprising a synchronized timing means for sensing contractions and expansions of the beating heart to be synchronized with the hand-held control means for creating the pockets.
 14. The apparatus of claim 13 wherein the synchronized timing means is a pressure transducer having a measuring device at its distal end connected to wiring for transmitting the pressure signal, said measuring device located on the surface of the excising assembly and the proximal end of the electrical wiring connected to the hand-held control means.
 15. The apparatus of claim 13 wherein the synchronized timing means is an EKG.
 16. The apparatus of claim 1 wherein the distance advanced within the organ or muscle is determined by a depth measurement means on the excising assembly.
 17. The apparatus of claim 1 wherein the optical fiber means has a diameter of 0.1 to 0.5 mm.
 18. The apparatus of claim 1 wherein said optical fiber means is connected to a Holmium HO:YAG laser source having a wavelength range of approximately 1.8 to 2.2 um and a power level range of approximately 0.2 J to 1.65 J.
 19. The apparatus of claim 1 wherein said optical fiber means comprises at least one central optical fiber having a diameter of around 0.2 mm. 